Prosthesis, delivery device and methods of use

ABSTRACT

Devices, systems and methods are described herein a prosthesis for implantation within a lumen or body cavity and delivery devices for delivering the prosthesis to a location for implantation. A delivery system can include a plurality of components which are moveable relative to each other. The delivery system can include a nose cone which can cover at least a first end of the prosthesis, an outer elongate member which can cover at least a second end of the prosthesis, and a tether which can at least partially restrain the prosthesis from deployment.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.14/628,034, filed Feb. 20, 2015, now U.S. Pat. No. 10,004,599, whichclaims priority to U.S. Provisional App. No. 61/943,270 filed Feb. 21,2014, titled PROSTHESIS DELIVERY DEVICE AND METHODS OF USE, U.S.Provisional App. No. 61/950,748 filed Mar. 10, 2014, titled PROSTHESIS,DELIVERY DEVICE AND METHODS OF USE, and U.S. Provisional App. No.62/004,637 filed May 29, 2014, titled PROSTHESIS, DELIVERY DEVICE ANDMETHODS OF USE, each of which is hereby incorporated herein by referencein its entirety and is to be considered a part of this specification.

BACKGROUND Field

Certain embodiments disclosed herein relate generally to prostheses forimplantation within a lumen or body cavity and delivery devices for aprosthesis. In particular, the prostheses and delivery devices relate insome embodiments to replacement heart valves, such as replacement mitralheart valves.

Background

Human heart valves, which include the aortic, pulmonary, mitral andtricuspid valves, function essentially as one-way valves operating insynchronization with the pumping heart. The valves allow blood to flowdownstream, but block blood from flowing upstream. Diseased heart valvesexhibit impairments such as narrowing of the valve or regurgitation,which inhibit the valves' ability to control blood flow. Suchimpairments reduce the heart's blood-pumping efficiency and can be adebilitating and life threatening condition. For example, valveinsufficiency can lead to conditions such as heart hypertrophy anddilation of the ventricle. Thus, extensive efforts have been made todevelop methods and apparatuses to repair or replace impaired heartvalves.

Prostheses exist to correct problems associated with impaired heartvalves. For example, mechanical and tissue-based heart valve prosthesescan be used to replace impaired native heart valves. More recently,substantial effort has been dedicated to developing replacement heartvalves, particularly tissue-based replacement heart valves that can bedelivered with less trauma to the patient than through open heartsurgery. Replacement valves are being designed to be delivered throughminimally invasive procedures and even percutaneous procedures. Suchreplacement valves often include a tissue-based valve body that isconnected to an expandable frame that is then delivered to the nativevalve's annulus.

Development of prostheses including but not limited to replacement heartvalves that can be compacted for delivery and then controllably expandedfor controlled placement has proven to be particularly challenging. Anadditional challenge relates to the ability of such prostheses to besecured relative to intralumenal tissue, e.g., tissue within any bodylumen or cavity, in an atraumatic manner.

Delivering a prosthesis to a desired location in the human body, forexample delivering a replacement heart valve to the mitral valve, canalso be challenging. Obtaining access to perform procedures in the heartor in other anatomical locations may require delivery of devicespercutaneously through tortuous vasculature or through open or semi-opensurgical procedures. The ability to control the deployment of theprosthesis at the desired location can also be challenging.

SUMMARY

Embodiments of the present disclosure are directed to a prosthesis, suchas but not limited to a replacement heart valve. Further embodiments aredirected to delivery systems, devices and/or methods of use to deliverand/or controllably deploy a prosthesis, such as but not limited to areplacement heart valve, to a desired location within the body. In someembodiments, a replacement heart valve and methods for delivering areplacement heart valve to a native heart valve, such as a mitral valve,are provided.

According to some embodiments, a delivery system can be used forcontrolled deployment of a prosthesis or replacement valve. In someembodiments, the delivery system can comprise a first member, a secondmember, and a tether. The first member can be configured to at leastpartially restrain a first end of the prosthesis or replacement valve.The second member can be configured to at least partially restrain asecond end of the prosthesis or replacement valve. The tether can beconfigured to at least partially encircle the prosthesis or replacementvalve and radially restrain at least a portion of the prosthesis orreplacement valve after the second member has been removed from thesecond end of the prosthesis or replacement valve. The tether can beconfigured to radially restrain at least a portion of the prosthesis orreplacement valve while the first member still at least partiallyrestrains the first end of the prosthesis or replacement valve.

According to some embodiments, the first member can comprise a firstshaft and the second member can comprise a second shaft, the secondshaft being positioned over the first shaft and slidable relative to thefirst shaft. The first member can comprise a nose cone configured toreceive and cover the first end of the prosthesis or replacement valve.The nose cone can be connected to a distal end of the first shaft. Thenose cone can comprise a proximally-facing opening to receive at least afirst end of the prosthesis or replacement valve. The nose cone cancomprise a taper towards the distal end of the nose cone. An outerdiameter of the nose cone can be similar to an outer diameter of thesecond shaft. An outer diameter of the nose cone is similar to an innerdiameter of the second shaft. The first member can comprise an innerretention ring configured to engage the first end of the prosthesis orreplacement valve. The inner retention ring can be connected to a distalportion of an inner retention shaft. The inner retention shaft can bepositioned between the first shaft and the second shaft and be slidablerelative to the first shaft. The inner retention ring can comprise ataper towards a proximal end of the inner retention ring. The innerretention ring can comprise a cavity at or near a distal end of theinner retention ring. The inner retention ring can comprise acompressible member received at least partially within the cavity, thecompressible member having a compressed diameter and an expandeddiameter.

According to some embodiments, the delivery system can comprise a tetherretention assembly configured to restrain the tether such that thetether can be tensioned to restrain at least a portion of the prosthesisor replacement valve. The tether retention assembly can comprise aninner component and an outer component. The outer component can beconfigured to cooperate with the inner component to restrain the tether.The inner component can comprise a C-lock. The outer component cancomprise a sheath. The outer component can be moveable relative to theinner component to release the tether. The tether retention assembly canfurther comprise a locking shaft. The outer component can be positionedat or near a distal end of the locking shaft. The locking shaft cancomprise a radial protrusion which can be configured to maintain radialalignment between the locking shaft and the second shaft. The lockingshaft can comprise a guide member for the tether.

According to some embodiments, the second member can comprise an outerelongate hollow member configured to cover at least the second end ofthe prosthesis or replacement valve. The outer elongate member can beconnected to a distal end of the second shaft. The outer elongate hollowmember can have a substantially constant diameter throughout theentirety of its length. The diameter of the outer elongate hollow membercan be substantially similar to a diameter of the second shaft The outerelongate hollow member can be moveable relative to the first member touncover the second end of the prosthesis or replacement valve while thefirst end of the prosthesis or replacement valve remains engaged to thefirst member. The delivery system can comprise an introducer sheathpositioned over the second shaft. The delivery system can comprise aplug, the plug being moveable to engage the first member when the firstmember is retrieved from a patient. The delivery system can comprise aplug shaft positioned between the first shaft and the second shaft andcan be slidable relative to the first shaft. The first shaft can behollow to receive a guidewire.

According to some embodiments, the delivery system can comprise aprosthesis or replacement valve, wherein a first end of the prosthesisor replacement valve engages the first member and a second end of theprosthesis or replacement valve engages the second member.

According to some embodiments, a delivery system can be used forcontrolled deployment of a prosthesis or replacement valve. The deliverysystem can comprise a nose cone shaft, a nose cone, an inner retentionshaft, an inner retention ring, a tether retention member, a lockingshaft, an outer elongate hollow member shaft, and an outer elongatehollow member. The nose cone can be connected to the distal end of thenose cone shaft. The nose cone can comprise a proximally-facing openingto receive at least a first end of the prosthesis or replacement valve.The inner retention shaft can be slidable over the nose cone shaft. Theinner retention ring can be connected to the distal end of the innerretention shaft. The inner retention ring can be configured to engagethe first end of the prosthesis or replacement valve. The tetherretention member can be on the inner retention shaft. The locking shaftcan be slidable over the inner retention shaft. The locking shaft can beconfigured to cooperate with the tether retention member to releasablyengage a tether attached to the prosthesis or replacement valve. Theouter elongate hollow member shaft can be slidable over the lockingshaft. The outer elongate hollow member can be connected to the distalend of the outer elongate hollow member shaft. The outer elongate hollowmember can have a proximal end and a distal end, the outer elongatehollow member being configured to cover at least the second end of theprosthesis or replacement valve when the first end of the prosthesis orreplacement valve is engaged with the inner retention ring and iscovered by the nose cone. The outer elongate hollow member can bemoveable relative to the nose cone to uncover the second end of theprosthesis or replacement valve while the first end of the prosthesis orreplacement valve remains engaged to the inner retention ring and iscovered by the nose cone.

According to some embodiments, the nose cone can comprise a tapertowards the distal end of the nose cone. An outer diameter of the nosecone can be similar to an outer diameter of at least one of the outerelongate hollow member shaft and the outer elongate hollow member. Anouter diameter of the nose cone can be similar to an inner diameter ofat least one of the outer elongate hollow member shaft and the outerelongate hollow member. The inner retention ring can comprise a tapertowards a proximal end of the inner retention ring. The inner retentionring can comprise a cavity at or near a distal end of the innerretention ring. The inner retention ring can comprise a compressiblemember received at least partially within the cavity, the compressiblemember having a compressed diameter and an expanded diameter. Thecompressed diameter can be approximately equal to an inner diameter ofthe nose cone and the expanded diameter can be greater than the innerdiameter of the nose cone. The locking shaft can comprise a radialprotrusion configured to maintain radial alignment between the lockingshaft and the outer elongate hollow member shaft. The locking shaft cancomprise a guide member for the tether. The outer elongate hollow membercan have a substantially constant diameter throughout the entirety ofits length. The diameter of the outer elongate hollow member can besubstantially similar to a diameter of the outer elongate hollow membershaft.

According to some embodiments, the delivery system can comprise anintroducer sheath having a proximal end and a distal end slidable overthe outer elongate hollow member shaft. The tether retention member cancomprise a C-lock. The delivery system can comprise a lock at the distalend of the locking shaft to cover the C-lock to releasably retain atether therein. The delivery system can comprise a plug shaft having aproximal end and a distal end. The plug shaft can be slidable over thelocking shaft and the outer elongate hollow member shaft can be slidableover the plug shaft. The delivery system can comprise a plug at thedistal end of the plug shaft to engage the nose cone when the nose coneis retrieved from a patient. The nose cone shaft can be hollow toreceive a guidewire.

According to some embodiments, the delivery system can comprise aprosthesis or replacement valve. A first end of the prosthesis orreplacement valve can engage the inner retention ring and can be coveredby the nose cone. A second end of the prosthesis or replacement valvecan be covered by the outer elongate hollow member shaft. A tether canbe connected to the tether retention member, the tether retention memberbeing covered by a lock at the distal end of the locking shaft, thetether wrapping at least partially around the prosthesis or replacementvalve and then extending proximally through at least the outer elongatehollow member shaft.

According to some embodiments, a method of delivery of a prosthesis orreplacement valve can comprise: delivering an intralumenal frameassembly to the in situ target location while the frame assembly is in aradially compacted state within an outer member, the frame assemblycomprising a frame having a first end, a second end and a longitudinalaxis extending between the first and second ends, the frame furthercomprising a tether encircling at least a portion of the frame, thetether configured to restrain the radial dimension of the frame; atleast partially removing the outer member from the frame assembly,wherein the tether restrains the radial dimension of the frame after theouter member is at least partially removed; and releasing the tetherfrom the frame to allow at least a portion of the frame assembly toradially expand.

According to some embodiments, releasing the tether from the frame canallow the second end of the frame to radially expand while the first endof the frame remains radially restrained. The method can compriseradially expanding the first end of the frame after releasing the tetherto allow the second end of the frame to radially expand. The first endof the frame, prior to radial expansion, can be restrained by a nosecone covering at least the first end of the frame. The outer member canbe at least partially removed from the frame assembly by moving theouter member relatively away from the nose cone. The outer member can beat least partially removed in a proximal direction from the frameassembly by moving the outer member relatively away from the nose cone.

According to some embodiments, the intralumenal frame assembly cancomprise a plurality of anchors at its second end, wherein the pluralityof anchors extend proximally away from the second end of the frameassembly as the outer member is moved proximally. The plurality ofanchors can flip to extend distally away from the second end of theframe assembly after the outer member uncovers the plurality of anchors.The tether can radially restrain the frame assembly during flipping ofthe anchors. The intralumenal frame assembly can comprise a replacementheart valve. The intralumenal frame assembly can be deliveredtransapically to a mitral valve location.

According to some embodiments, a delivery system can be used forcontrolled deployment of a prosthesis or replacement valve. The deliverysystem can comprise a delivery catheter, a prosthesis and a cover. Thecover can be positioned over a plurality of first anchors of theprosthesis while the first anchors move from pointing in a firstlongitudinal direction to a second longitudinal direction, therebypreventing or limiting contact between the first anchors and tissue.

In some embodiments, the prosthesis or replacement valve can comprise aradially compacted replacement valve having a longitudinal axispositioned within the delivery catheter and comprising a plurality offirst anchors wherein the first anchors each have an end pointing in afirst longitudinal direction in the radially compacted state and the endis configured to change direction to point in a second longitudinaldirection, the ends pointing in the second longitudinal direction afterthe replacement valve is deployed from the delivery catheter.

In some embodiments, a delivery system can be used for controlleddeployment of a replacement valve. The delivery system can comprise asheath and an expandable cover. The sheath can be configured to surrounda radially compacted replacement valve, wherein retraction of the sheathfrom off of the radially compacted replacement valve allows the radiallycompacted replacement valve to at least partially expand. The expandablecover can be advanceable over the sheath prior to retraction to allowfor expansion of the replacement valve within the expandable cover asthe sheath is retracted to prevent or limit contact between theexpanding replacement valve and tissue.

In certain embodiments, a replacement valve can comprise a plurality ofanchors that are configured to change direction during expansion. Eachof the anchors can have an end, the end pointing in a first directionprior to expansion and in a second direction after at least partialexpansion. Each anchor can rotate at least 45 degrees during the partialexpansion.

The delivery device can be used in a number of different methods, forexample, a method of delivery of a replacement valve. A method cancomprise: advancing a delivery system holding a radially compactedreplacement valve to a native valve, the delivery system comprising: asheath surrounding the radially compacted replacement valve; and anexpandable cover; withdrawing the sheath to allow the replacement valveto at least partially expand within the expandable cover to prevent orlimit contact between the expanding replacement valve and tissue.

In certain embodiments, advancing can further comprise advancing thedelivery system to the native valve transapically. An additional stepcan be advancing the expandable cover over the sheath.

According to certain embodiments, a method of delivery of a replacementvalve can comprise: advancing a delivery system holding a radiallycompacted replacement valve to a native valve, the delivery systemhaving a longitudinal axis; at least partially expanding the replacementvalve radially outward from the longitudinal axis and within anexpandable cover to prevent or limit contact between the expandingreplacement valve and tissue.

At least partially expanding the replacement valve can comprise allowinga plurality of anchors to self-expand within the expandable cover.Allowing the plurality of anchors to self-expand can comprise flippingan end of each of the anchors of the plurality of anchors to change alongitudinal orientation of the end from a first longitudinal directionto a second opposite longitudinal direction.

A delivery system can be used for controlled deployment of a prosthesis.In some embodiments, the delivery system can include an elongate innermember, an inner retention mechanism on the elongate inner member, and ashaft assembly. The inner retention mechanism can be configured toengage the prosthesis. The shaft assembly can be slidable over theelongate inner member and the inner retention mechanism. The shaftassembly can comprise an outer retention member, a first member and asecond member. The outer retention member, together with the innerretention mechanism can be configured to secure the prosthesis on thedelivery system. The first and second members can both be connected tothe outer retention member and can facilitate delivery of the prosthesiswith stretch and compression resistance while retaining the prosthesisduring delivery through tortuous pathways.

In accordance with some embodiments a delivery system can comprise anelongate inner member and a shaft assembly configured to be slidableover the elongate inner member. The shaft assembly can be configured toat least partially radially constrain an expandable prosthesis when theexpandable prosthesis is provided over the elongate inner member, andthe shaft assembly can comprise a compression member and a tensionmember concentrically arranged.

In some embodiments, the compression member can surround the tensionmember. The delivery system can comprise an outer sheath configured tobe slidable over the shaft assembly. The outer sheath can be configuredto cover a distal end of the expandable prosthesis when the expandableprosthesis is provided over the elongate inner member. The outer sheathcan comprise a slotted hypo tube. The slotted hypo tube can beconfigured to surround the compression member and the tension memberwhen the outer sheath covers the distal end of the expandableprosthesis. At least a segment of the outer sheath can be formed ofePTFE.

In some embodiments, a flexible delivery system can comprise an elongateinner member, an inner retention mechanism on the elongate inner member,a mid shaft assembly, and an outer sheath. The delivery system cancomprise a handle. The inner retention mechanism can be configured toengage a radially compacted proximal end of a replacement mitral valve.The mid shaft assembly can be configured to be slidable over theelongate inner member and the inner retention mechanism. The mid shaftassembly can comprise an outer retention member configured to cover atleast the radially compacted proximal end of the replacement mitralvalve when the proximal end of the replacement mitral valve is engagedwith the inner retention mechanism, a first member having a distal endconnected to the outer retention member, and a second member having adistal end connected to the outer retention member and extending alongthe length of the first member. The outer sheath can be configured to beslidable over the mid shaft assembly and configured to cover the distalend of the replacement mitral valve. The first member and second membercan be positioned between the handle and the outer retention member.

In some embodiments, a delivery system can be configured to retain atleast a radially compacted proximal end of a replacement mitral valvebetween an inner retention mechanism and an outer retention memberduring advancement of the delivery system within the body and the firstand second members facilitate advancement with stretch and compressionresistance through long and tortuous pathways.

In some embodiments, the first member can comprise a compression member.The first member can comprise a coiled spring. The second member cancomprise a tension member. The second member can comprise a braidedwire. The elongate inner member can comprise a tube having a lumen sizedand configured to slidably accommodate a guidewire. The delivery systemcan comprise a nose cone connected to the distal end of the elongateinner member. The inner retention mechanism can comprise a ringcomprising a plurality of teeth configured to engage tabs on theproximal end of the prosthesis. The outer retention member can be aring.

In some embodiments, the delivery system can comprise a replacementmitral valve having a proximal end and a distal end. The proximal end ofthe replacement mitral valve can be engaged with the inner retentionmechanism on the elongate inner member and can be covered by the outerretention member. The distal end of the replacement mitral valve can becovered by the outer sheath. The outer sheath can comprise a slottedhypo tube. The mid shaft assembly can comprise a plastic tube, whereinboth the compression member and the tension member can be connected tothe plastic tube. The plastic tube can be positioned between the handleand the compression and tension members.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects and advantages are described belowwith reference to the drawings, which are intended to illustrate but notto limit the invention.

FIG. 1 shows an embodiment of a delivery system.

FIGS. 2-4 illustrates steps of a deployment method using the deliverysystem of FIG. 1.

FIGS. 5 and 6 show a perspective and side view of an embodiment of aprosthesis in a pre-expanded state.

FIGS. 7 and 8 show a perspective and side view of the prosthesis in anexpanded state.

FIG. 9 shows another embodiment of a delivery system.

FIG. 10 shows a close-up in view of components of the delivery system ofFIG. 9.

FIGS. 11 and 12 show components of the delivery system of FIG. 9 withcertain components having been omitted.

FIG. 13 shows further components of the delivery system of FIG. 9 withadditional components having been omitted.

FIGS. 14-23 illustrate steps of a deployment method using the deliverysystem of FIG. 9.

FIG. 24 illustrates a schematic representation of a prosthesispositioned within the heart.

FIG. 25 shows another embodiment of a delivery system.

FIG. 26 shows a cross-sectional view of the delivery system of FIG. 25.

FIG. 27 shows another embodiment of an inner retention mechanism.

FIG. 28 shows a cross-sectional view of the inner retention mechanism ofFIG. 27.

FIG. 29 shows a cross-sectional view of an embodiment of the innerretention mechanism and nose cone in a first configuration.

FIG. 30 shows a cross-sectional view of the inner retention mechanismand nose cone of FIG. 29 in a second configuration.

FIG. 31 shows an embodiment of a delivery system.

FIG. 32 is an exploded view of the distal end of the delivery system ofFIG. 31.

FIG. 33 is a cross-section view of the distal end of the delivery systemof FIG. 31.

FIG. 34 shows an exploded view of a mid shaft assembly that may be usedin the delivery system of FIG. 31.

FIGS. 35A-C illustrates a distal end of the delivery system of FIG. 31in a series of positions.

FIGS. 36A-C show a handle of the delivery system of FIG. 31 in a seriesof positions.

FIG. 37 shows a prosthesis within a delivery system.

FIG. 38 is a schematic representation showing an access path into theheart.

FIG. 39 illustrates a replacement heart valve deployed in the mitralvalve between the left atrium and the left ventricle.

FIGS. 40A-B illustrate another embodiment of a delivery system.

DETAILED DESCRIPTION

The present specification and drawings provide aspects and features ofthe disclosure in the context of several embodiments of replacementheart valves, delivery devices and methods that are configured for usein the vasculature of a patient, such as for replacement of naturalheart valves in a patient. These embodiments may be discussed inconnection with replacing specific valves such as the patient's aorticor mitral valve. However, it is to be understood that the features andconcepts discussed herein can be applied to products other than heartvalve implants. For example, the controlled positioning, deployment, andsecuring features described herein can be applied to medical implants,for example other types of expandable prostheses, for use elsewhere inthe body, such as within an artery, a vein, or other body cavities orlocations. In addition, particular features of a valve, delivery device,etc. should not be taken as limiting, and features of any one embodimentdiscussed herein can be combined with features of other embodiments asdesired and when appropriate. While certain of the embodiments describedherein are described in connection with a transapical delivery approach,and certain of the embodiments described herein are described inconnection with a transfemoral delivery approach, it should beunderstood that these embodiments can be used for other deliveryapproaches. Moreover, it should be understood that certain of thefeatures described in connection with some embodiments can beincorporated with other embodiments, including those which are describedin connection with different delivery approaches.

With reference to FIG. 1, an embodiment of a delivery device or system10 is shown. The delivery system can be used deploy a prosthesis, suchas a replacement heart valve, within the body. Replacement heart valvescan be delivered to a patient's heart mitral valve annulus in variousways, such as by open surgery, minimally-invasive surgery, andpercutaneous or transcatheter delivery through the patient'svasculature. The delivery device 10 can be relatively short to moreeasily be used in an open heart procedure or other more directprocedures than the percutaneous procedure starting at the leg. At thesame time, the delivery device 10 can still be relatively flexible toallow, for example, advancement through the pulmonary veins or the wallof the left atrium and then bending of the delivery device for properplacement at the mitral valve. In this way the illustrated embodimentcomprises an elongate, delivery system configured to be advanced in atransapical delivery approach.

The delivery system 10 can include an elongate shaft assembly 12comprising a proximal end and a distal end, wherein a handle (not shown)is coupled to the proximal end of the assembly 12. The elongate shaftassembly 12 can be used to hold the prosthesis for advancement of thesame through the vasculature to a treatment location. The elongate shaftassembly 12 can include an implant retention area 16 that can be usedfor this purpose. In some embodiments, the elongate shaft assembly 12can hold an expandable prosthesis in a compressed state at implantretention area 16 for advancement of the prosthesis within the body. Theelongate shaft assembly 12 may then be used to allow controlledexpansion of the prosthesis at the treatment location. The implantretention area 16 is shown at the distal end of the delivery device, butmay also be at other locations.

The elongate shaft assembly 12 can include one or more subassemblies aswill be described in more detail below. The elongate shaft assembly 12can be configured to deliver a prosthesis positioned within the implantretention area 16 to a treatment location. One or more of thesubassemblies can then be moved to allow the prosthesis to be releasedat the treatment location. For example, one or more of the subassembliesmay be movable with respect to one or more of the other subassemblies.The handle can include various control mechanisms that be used tocontrol the movement of the various subassemblies. In this way, theprosthesis can be controllably loaded onto the delivery device 10 andthen later deployed within the body.

With continued reference to FIG. 1, it can be seen that thesubassemblies of the elongate shaft assembly 12 can include one or moreouter sheaths 14, a cover 20, a capsule 24, and a nose cone 28. Animplant in a pre-deployed state can be held by the delivery devicewithin the capsule and the nose cone. The capsule and nose cone can bemade of polyurethane for atraumatic entry and to minimize injury totissue. The nose cone or other parts can also be radiopaque to providefor visibility under fluoroscopy.

The implant or prosthesis can take any number of different forms. Aparticular example of frame for a prosthesis is shown herein, though itwill be understood that other designs can also be used. Additionalexample designs for a prosthesis are described in U.S. Pat. Nos.8,403,983, 8,414,644, 8,652,203 and U.S. Patent Publication Nos.2011/0313515, 2012/0215303, 2014/0277390, 2014/0277422, 2014/0277427,the entirety of these patents and publications are hereby incorporatedby reference and made a part of this specification.

Each of the subassemblies can be made of or attached to tubes that slidewithin one another. In this way, each of the outer sheaths 14, cover 20,capsule 24, and/or nose cone 28 may move with respect to one or more ofthe other components or subassemblies. The innermost assembly mayinclude a lumen sized and configured to slidably accommodate a guidewireso that the delivery device 10 can be advanced over the guidewire.

The various tubes can be a hypodermic tube or hypo tube. The tube can bemade from one of any number of different materials including nitinol,stainless steel, and medical grade plastics. The tube can be a singlepiece tube or multiple pieces connected together. Using a tube made ofmultiple pieces can allow the tube to provide different characteristicsalong different sections of the tube, such as rigidity and flexibility.For example, in some embodiments it can be desirable, and/or needful,for the delivery device 10 to have greater flexibility at the distal endof the device, where flexibility is not as necessary for the proximalend.

Moving now to FIG. 2, it can be seen that the cover 20 can be advancedover the capsule 24. The cover 20 can be used to allow the implant toexpand while reducing and/or preventing contact between the implant andbody tissue during all or part of the expansion process. The cover 20can be made of a plurality of longitudinal struts sufficiently rigid toadvance over the capsule after the delivery device has been positionedwithin the body at or near a treatment location. For example, thedelivery device can be advanced into the left ventricle of the heart fora mitral valve replacement and the cover can then be advanced over thecapsule prior to expanding all or part of the implant. The cover canalso include a film, sheet, fabric, or other material that can bepositioned between the struts. This sheet may or may not be flexible.The sheet can initially be folded within an outer sheath and can expandto a larger size after advancing over the capsule. It will also beunderstood that in other embodiments, the cover can be positioned overthe capsule in an initial state, or prior to advancing the deliverydevice to the treatment area.

Once the cover is in position, or while the cover is being advanced intoposition, the capsule 24 can be withdrawn or otherwise removed fromcovering the implant 30. Removing the capsule can allow the implant toexpand, partially or in full. In some embodiments, a separate device cancontrol all or part of the expansion of the implant. FIG. 3 shows thecover 20 over the implant 30 and the capsule 24 withdrawn. Withdrawingthe capsule can also assist the cover in expanding so as not to impedeor restrict expansion of the implant. With the implant partially orfully expanded, the cover can then be withdrawn. FIG. 4 shows thedelivery device after the cover has been withdrawn, with the implantpartially expanded. FIG. 4 also shows a tether, wire or suture 32 thatcan be used to at least partially control expansion of the implant.Also, an end portion of the implant remains compacted in the nose cone28. This can allow the implant to be positioned at a heart locationprior to full expansion.

FIG. 4 also illustrates that the implant 30 has a plurality of anchors34. In some embodiments, the anchors 34 can point in a first directionprior to expansion and then rotate to point in a second, longitudinallyopposite direction after expansion. The anchors can completely flipdirections. The cover 20 can beneficially ensure that the anchors do notengage or get caught in tissue during rotation. For example, without acover during deployment in the left ventricle of the heart, the anchorscan easily get caught in the chordae tendineae as they rotate or changedirections. FIG. 4 further illustrates that the tether, wire or suture32 may extend from within the capsule 24 and wrap around the implant 30,for example at the base of the anchors 34. The tether, wire or suture 32may thus partial control expansion of the implant by radiallyrestraining expansion of the implant as the anchors 34 are released fromthe capsule 24.

FIGS. 5-8 illustrate an example implant 30 that can be used with thedelivery device 10. It can be seen that the anchors 34 can point in afirst direction prior to deployment when in the pre-deployment state ofFIGS. 5-6. When deployed, the anchors can rotate to the position shownin FIGS. 7-8. It will be understood that the implant can be made of aself-expanding material so as to self-expand into the desired shape. Theimplant of FIGS. 5-6 can be cut from a tube to the shape shown and theexpanded to the shape of FIGS. 7-8. The implant can then be compressedback to the shape shown in FIGS. 5-6 or to a similar shape. Furtherdetails of the implant are described in the patents and applicationsincorporated by reference above.

The embodiment of FIGS. 9-13 illustrates a delivery device or system100. Delivery system 100 can have components, features, and/orfunctionality similar to those described with respect to delivery deviceor system 10. The delivery system 100 can be used to deploy aprosthesis, such as a replacement heart valve as described elsewhere inthis specification, within the body. The delivery system 100 can receiveand/or cover portions of the prosthesis such as a first end and secondend of the prosthesis. For example, the delivery system 100 may be usedto deliver a prosthesis 30 such as illustrated in FIGS. 7 and 8, wherethe prosthesis includes a first end 33 and a second end 31, and whereinthe second end 31 is configured to be deployed before the first end 33.Replacement heart valves can be delivered to a patient's heart mitralvalve annulus or other heart valve location in various ways, such as byopen surgery, minimally-invasive surgery, and percutaneous ortranscatheter delivery through the patient's vasculature. The deliverysystem 100 can be relatively short to more easily be used in an openheart procedure or other more direct procedures than the percutaneousprocedure starting at the leg. At the same time, the delivery system 100can still be relatively flexible to allow, for example, advancementthrough the pulmonary veins or the wall of the left atrium and thenbending of the delivery device for proper placement at the mitral valve.In some embodiments, the delivery system 100 is particularly suitablefor delivering a replacement heart valve to a mitral valve locationthrough a transapical approach (e.g., through the apex of the heart).

With reference first to the embodiment of FIGS. 9 and 10, the deliverysystem 100 can include a handle 110 and a plurality of sheaths and/orshafts such as the illustrated introducer sheath 112 and outer elongatehollow member shaft 114. As will be described in further detail below,the plurality of shafts can be sized and shaped to be slidable relativeto each other. Accordingly, it should be understood that one or more ofthe plurality of shafts can be concentric with respect to another of theshafts to facilitate slidable movement of the shafts relative to eachother. The plurality of shafts can be coupled to one or more othercomponents of the delivery system 100. In some embodiments, the handle110 can include a plurality of switches, levers, or other actuatablemechanisms which can be used to control the movement of the one or moreshafts of the delivery system 100 and/or to control the operation ofother components of the delivery system 100.

With continued reference to the embodiment of FIGS. 9 and 10, thedelivery system 100 can include an introducer sheath 112 and an outerelongate hollow member shaft 114, each having a proximal and distal end.As used to describe the components of the delivery system, “proximal”refers to a location of the component that is closer to the handle 110,and “distal” refers to a location of the component that is further fromthe handle 110. In some embodiments, the proximal end of the introducersheath 112 can be coupled to the handle 110. The introducer sheath 112can be sized and shaped such that introducer sheath 112 is slidable overthe outer elongate hollow member shaft 114. For example, in someembodiments, the introducer sheath 112 can be fixed relative to thehandle 110 and the outer elongate hollow member shaft 114 can be movedwithin the introducer sheath 112. In some embodiments, the introducersheath 112 can be movable relative to the handle 110. As should beunderstood from the above disclosure, in some embodiments, theintroducer sheath 112 can be omitted and the outer elongate hollowmember shaft 114 can form the outer shaft of the delivery system 100.For example, the embodiment of FIGS. 25 and 26 illustrates a deliverysystem 200 without an introducer sheath 112 and the outer elongatehollow member shaft 214 forming an outer shaft.

With continued reference to the embodiment of FIGS. 9 and 10, the outerelongate hollow member shaft 114 can optionally have a distal endcoupled to a proximal end of an outer elongate hollow member 116. Theouter elongate hollow member 116 can be a sheath or capsule similar tocapsule 24 described in connection with delivery system 10. In someembodiments, the outer elongate hollow member shaft 114 and/or the outerelongate hollow member 116 can cover at least a portion of theprosthesis while the prosthesis is being delivered to the deploymentsite. For example, the outer elongate hollow member shaft 114 and/or theouter elongate hollow member 116 can cover at least the second end 31 ofthe prosthesis while the first end 33 of the prosthesis is receivedwithin nose cone 118. In some embodiments, the outer elongate hollowmember 116 can also cover the first end of the prosthesis. The outerelongate hollow member 116 can be sized and shaped such that theelongate hollow member 116 can retain the prosthesis in a compressedstate as it is delivered to the deployment site. Accordingly, the outerelongate hollow member shaft 114 can function as a capsule shaft.Optionally, the anchors 34 on the prosthesis may extend proximallytoward the handle 110 when the prosthesis is covered by the outerelongate hollow member. The outer elongate hollow member 116 can bemoveable relative to the nose cone 118 to uncover the second end of theprosthesis while the first end of the prosthesis remains engaged to aninner retention member (described with respect to FIG. 13 below) withinthe nose cone 118 and remains covered by the nose cone 118.

As shown in the illustrated embodiment, the outer elongate hollow member116 includes a taper at a proximal end such that the proximal end of theouter elongate hollow member 116 has an outer diameter which is lessthan an outer diameter of the distal end of the outer elongate hollowmember 116. In some embodiments, the outer diameter of the proximal endof the outer elongate hollow member 116 can be similar to, or equal to,the outer diameter of a distal end of the outer elongate hollow membershaft 114. In some embodiments, the outer elongate hollow member 116 canbe collapsible such that, upon retraction towards the introducer sheath112, the outer elongate hollow member 116 can collapse into theintroducer sheath 112. The outer elongate hollow member 116 can beformed from a variety of materials, including ePTFE, as well as otherbiocompatible materials.

With reference to the embodiment of FIGS. 25 and 26, in someembodiments, the outer elongate hollow member shaft 214 can extend overthe prosthesis and can be sized and shaped such that it can retain theprosthesis in a compressed state as it is delivered to the deploymentsite. As shown in the illustrated embodiment, the outer elongate hollowmember shaft 214 can have a constant or substantially constant outerdiameter throughout the entirety, or a substantial portion of theentirety, of its length.

As shown more clearly in FIG. 26, the outer elongate hollow member shaft214 can have a taper at its distal end. The outer elongate hollow membershaft can include a marker 217 positioned proximate the distal end. Insome embodiments, the outer elongate hollow member shaft 214 can includea first portion 215 and a second portion 216. This can advantageouslyallow for the use of two types of material for the outer elongate hollowmember shaft 214. For example, as shown in the illustrated embodiment,at least a portion of the first portion 215 can be positioned radiallyoutward from of the second portion 216 relative to a longitudinal axisof the outer elongate hollow member shaft 214. The first portion 215 canbe formed from a relatively rigid material, such as PEBAX, ULTEM, PEAKand any other biocompatible material as desired. This can advantageouslyprovide some degree of rigidity for the outer elongate hollow membershaft 214. The second portion 216 can be formed from a more compliantmaterial, such as PTFE, ePTFE and any other biocompatible material asdesired. This can advantageously provide a more compliant inner surfacefor the outer elongate hollow member shaft 214, which can be beneficialwhen contacting other components of the delivery system 200 and theprosthesis. In some embodiments, the second portion 216 can be a linerwhich is applied to the first portion 215.

While the illustrated outer elongate hollow member shaft 214 is shownwith multiple portions formed from multiple materials, it is alsocontemplated that the outer elongate hollow member shaft 214 can be aformed from a single material. Moreover, in some embodiments, the outerelongate hollow member shaft 214 can include an elongate hollow membersimilar to outer elongate hollow member 116 which can cover at least aportion of the prosthesis. In some embodiments, the outer elongatehollow member can have a constant or substantially constant outerdiameter throughout the entirety, or a substantial portion of theentirety, of its length. The outer diameter of the outer elongate hollowmember can be similar to, or equal to, the outer diameter of the outerelongate hollow member shaft 214. In some embodiments, the outerelongate hollow member can be formed from a material different from theouter elongate hollow member shaft 214.

With reference now to the embodiment of FIGS. 11 and 12, whichillustrates delivery system 100 without the outer elongate hollow member116 being shown, the delivery system 100 can include a plug shaft 120, alocking shaft 122, and an inner retention shaft 124, each having aproximal and distal end. The distal end of plug shaft 120 can be coupledto the proximal end of a plug 126. In some embodiments, plug shaft 120can be sized and shaped such that plug shaft 120 is slidable over thelocking shaft 122. For example, in some embodiments, the locking shaft122 can be moved within the plug shaft 120. In some embodiments, theplug shaft 120 can be moved over the locking shaft 122. Moreover, plugshaft 120 can be sized and shaped such that the outer elongate hollowmember shaft 114 is slidable over the plug shaft 120. In someembodiments, the plug 126 can be used to engage the nose cone when thenose cone is retrieved from the patient. For example, the plug 126 canbe used to contact the proximal end of the nose cone 118 as the nosecone 118 is retracted proximally toward the plug 126 or as the plug 126is advanced distally toward the nose cone 118. As should be understoodfrom the above disclosure, in some embodiments, the plug shaft 120and/or the plug 126 can be omitted from the delivery system 100. Forexample, the embodiment of FIGS. 25 and 26 illustrates a delivery system200 without a plug shaft 120 or plug 126.

With reference back to the embodiment of FIGS. 11 and 12, the nose cone118 can have a tapered distal end. The nose cone 118 can be formed froma relatively rigid, high durometer material such as a metal. The nosecone 118 can have a length, measured from the distalmost end to aproximalmost end, of between approximately 5 mm to 50 mm, betweenapproximately 10 mm to approximately 40 mm, between approximately 15 mmto approximately 25 mm, approximately 20 mm, any other lengths withinthese ranges, and any other lengths as desired.

In some embodiments such as that of FIGS. 25 and 26, the nose cone 218can have a more elongated shape. As shown in the illustrated embodiment,the tapered portion can be concave thereby forming a more defined distaltip of the nose cone 218. As shown more clearly in FIG. 26, the nosecone 218 can include a first portion 219 and a second portion 220. Thiscan advantageously allow for the use of two types of material for thenose cone 218. For example, as shown in the illustrated embodiment, atleast a portion of the first portion 219 can be positioned radiallyoutward from of the second portion 220 relative to a longitudinal axisof the nose cone 218. The first portion 219 can be formed from a lowerdurometer material such as urethane, PEBAX, polysilicone and any otherbiocompatible material as desired. The second portion 220 can be formedfrom higher durometer materials such as stainless steels, titanium, andany other biocompatible material as desired. This can advantageouslyprovide additional structural support for the nose cone 218. In someembodiments, the second portion 220 can include threading for attachmentto a shaft, such as nose cone shaft 130. In some embodiments, the firstportion 219 can be overmolded onto the second portion 220 and/orattached using mechanical fasteners such as screws, bolts, rivets, andthreaded couplings, chemical fasteners, such as adhesives, or othertypes of fastening techniques such as welding. In some embodiments, thenose cone 218 can be a single unit formed from a single material.

With reference particularly to the embodiment of FIG. 26, the outerdiameter of the nose cone 218, such as the first portion 219 and/orsecond portion 220, can be similar to, or equal to, the outer diameterof an outer shaft and/or outer component, such as the outer elongatehollow member shaft 214. As shown in the illustrated embodiment, thefirst portion 219 has an outer diameter which is similar to that of theouter elongate hollow member shaft 214. This can form a generally smoothtransition in diameter between the nose cone 218 and the outer shaftand/or the outer component if and when the nose cone 218 is brought intocontact with the outer shaft and/or the outer component. In someembodiments, the nose cone 218 can have an outer diameter ofapproximately 31 Fr or 32 Fr and the outer shaft and/or outer componentcan have an outer diameter of approximately 31 Fr or 32 Fr.

In some embodiments, the outer diameter of the nose cone 218, such asthe first portion 219 and/or second portion 220, can be similar to, orequal to, the inner diameter of an outer shaft and/or outer componentsuch that the first portion 219 and/or the second portion 220 can bepartially received within the outer shaft and/or outer component. Insome embodiments, the nose cone 218 can have an outer diameter ofapproximately 30 Fr and the outer shaft and/or outer component can havean inner diameter of approximately 30 Fr. In some embodiments, the outershaft can be an outermost shaft of the delivery system.

With reference back to the embodiment of FIGS. 11 and 12, the distal endof locking shaft 122 can be coupled to at least a portion of a tetherretention assembly 128. As shown in the illustrated embodiment, thelocking shaft 122 is coupled to a lock 129 of the tether retentionassembly 128. Lock 129 can function as a sheath of the tether retentionassembly 128. The lock 129 can be used to cover a correspondingcomponent of the tether retention assembly 128 such as a tetherretention member 134, not shown in FIGS. 11 and 12 but which will bedescribed in further detail below with respect to FIG. 13. In someembodiments, locking shaft 122 can be sized and shaped such that lockingshaft 122 is slidable over the inner retention shaft 124. For example,in some embodiments, the inner retention shaft 124 can be moved withinthe locking shaft 122. In some embodiments, the locking shaft 122 can bemoved over the inner retention shaft 124. The locking shaft 122 cancooperate with the tether retention assembly 128 to release a tether 136(shown in FIG. 13) attached to the prosthesis. For example, proximalmovement of locking shaft 122 can result in proximal movement of thelock 129 relative to the tether retention member thereby releasing atether engaged to the tether retention assembly 128. Moreover, lockingshaft 122 can be sized and shaped such that the outer elongate hollowmember shaft 114 is slidable over the locking shaft 122.

With continued reference to the embodiment of FIGS. 11 and 12, thedistal end of the inner retention shaft 124 can be coupled to at least aportion of an inner retention member 132 that is positioned within nosecone 118 (not shown in FIGS. 11 and 12, but shown in FIG. 13). In someembodiments, inner retention shaft 124 can be sized and shaped such thatinner retention shaft 124 is slidable within the locking shaft 122. Forexample, in some embodiments, the inner retention shaft 124 can be movedwithin the locking shaft 122. In some embodiments, the locking shaft 122can be moved over the inner retention shaft 124. The inner retentionshaft 124 can cooperate with the inner retention member 132 and the nosecone 118 to release a first end of the prosthesis from the nose cone118. In some embodiments, the first end of the prosthesis can bereceived within a proximally-facing opening 119 (see FIG. 11) andcovered by the nose cone 118. The first end of the prosthesis can alsobe engaged with the inner retention member 132. Accordingly, proximalmovement of the inner retention shaft 124 can result in proximalmovement of the inner retention member relative to the nose cone 118which can release the first end of the prosthesis from the nose cone118. Similarly, distal movement of the nose cone 118 relative to theinner retention shaft 124, and thus the inner retention member, can alsorelease the first end of the prosthesis from the nose cone 118.

In some embodiments such as that of FIG. 26, the inner locking shaft 222can include a radial protrusion 224, such as an annular disc, and a lock229 similar to lock 129. The radial protrusion 224 can assist inmaintaining the locking shaft 222 in a desired radial alignment relativeto the shaft within which the locking shaft 222 is positioned. Forexample, as shown in the illustrated embodiment, the radial protrusioncan assist in maintaining concentricity between the locking shaft 222and another shaft such as the outer elongate hollow member shaft 214 inembodiments without a plug shaft 120 and/or plug 126. In someembodiments, the locking shaft 222 can include a guide member 226 forthe tether, wire or suture 32. As shown in the illustrated embodiment,the guide member can be formed as a hole on the radial protrusion.

In some embodiments, the locking shaft 222 can be retracted via use of aspring loaded actuator. The spring loaded actuator can be similar tospring 1066 described in connection with FIG. 36C.

With reference now to the embodiment of FIG. 13, which illustratesdelivery system 100 without the outer elongate hollow member 116, nosecone 118, locking shaft 122, and lock 129 being shown, the deliverysystem 100 can include a nose cone shaft 130 having a proximal anddistal end. The distal end of the nose cone shaft 130 can be coupled toa portion of the nose cone 118. In some embodiments, nose cone shaft 130can be sized and shaped such that inner retention shaft 124 is slidableover the nose cone shaft 130. For example, in some embodiments, the nosecone shaft 130 can be moved within the inner retention shaft 124. Insome embodiments, the inner retention shaft 124 can be moved over thenose cone shaft 130. Moreover, in some embodiments, the nose cone shaft130 can be hollow such that the nose cone shaft 130 can receive aguidewire.

With continued reference to the embodiment of FIG. 13, the deliverysystem 100 can include an inner retention member 132 such as an innerretention ring coupled to the distal end of the inner retention shaft124. The inner retention member 132 can include a plurality of slotssized and shaped to receive portions of a first end of the prosthesis.In some embodiments, the slots can extend radially inward. The first endof the prosthesis can be placed in a compressed state such that thefirst end of the prosthesis is retained between the inner retentionmember 132 and the nose cone (not shown) when the inner retention member132 is received within and covered by the nose cone. In someembodiments, when the inner retention member 132 is uncovered, the firstend of the prosthesis can expand radially outward from the innerretention member 132 and thereby disengage from the inner retentionmember 132.

In some embodiments such as that of FIGS. 27 and 28, the inner retentionmember 232 can have a more elongated design. As shown in the illustratedembodiment, the inner retention member 232 can have a proximal end 234and a distal end 236 with a plurality of slots 238 sized and shaped toreceive portions of a first end of the prosthesis positioned proximatethe proximal end 234. Slots 238 can extend along a longitudinal axis ofthe inner retention member 232. In some embodiments, the inner retentionmember 232 can include a cavity 239 positioned distal the slots 238. Thecavity 239 can be sized and shaped to receive portions of the first endof the prosthesis. As shown in the illustrated embodiment, the cavity239 can have an annular shape. In some embodiments, the inner retentionmember 232 can include a taper towards the proximal end 234. This canfacilitate removal of the inner retention member 232 from the heart byreducing the diameter at the proximalmost end of the inner retentionmember 232 and reducing the likelihood of snagging on tissue. This canbe particularly advantageous in embodiments where the plug shaft 120and/or plug 126 are not included in the delivery system 100.

As shown in the illustrated embodiment, the inner retention member 232can include a cavity 240 proximate the distal end 236. The cavity 240can be formed between one or more radial protrusions, such as ridges244, 246. A compressible member 242, such as an O-ring, can be receivedat least partially within the cavity 240. As shown in the illustratedembodiment, the cavity 240 can have an annular shape.

With continued reference to the embodiment of FIG. 28, in someembodiments the inner retention member 232 can include a first portion248 and a second portion 250. This can advantageously allow for the useof two types of material for the inner retention member 232. Forexample, as shown in the illustrated embodiment, at least a portion ofthe first portion 248 can be positioned radially outward from of thesecond portion 250 relative to a longitudinal axis of the innerretention member 232. The first portion 248 can be formed from materialssuch as urethane, PEBAX, polysilicone and any other biocompatiblematerial as desired. The second portion 250 can be formed from higherdurometer materials such as stainless steels, titanium, and any otherbiocompatible material as desired. In some embodiments, the secondportion 250 can include threading for attachment to a shaft, such asinner retention shaft 124. This can advantageously provide additionalstructural support for the inner retention member 232. In someembodiments, the first portion 248 can be overmolded onto the secondportion 250 and/or attached using mechanical fasteners such as screws,bolts, rivets, and threaded couplings, chemical fasteners, such asadhesives, or other types of fastening techniques such as welding. Insome embodiments, the inner retention member 232 can be a single unitformed from a single material.

As shown in the embodiment of FIG. 29, in some embodiments thecompressible member 242 can be sized and shaped such that it can becompressed to a smaller outer diameter. This can allow the compressiblemember 242 to fit within the nose cone, such as nose cones 118, 218,when the inner retention member 232 is positioned within the nose cone218. In such an embodiment, positioning within the nose cone 218 canmaintain the compressible member 242 in this compressed state. Once thecompressible member 242 is no longer fully positioned within the nosecone 218, as shown in the embodiment of FIG. 30, the compressible member242 can expand to a larger outer diameter. In some embodiments, theouter diameter in the relaxed or expanded state can be greater than theinner diameter of the nose cone 218. In some embodiments, the outerdiameter in the relaxed or expanded state can be greater than the outerdiameter of the nose cone 218. This can advantageously facilitateremoval of the inner retention member 232 and nose cone 218 from theheart. For example, the compressible member can be positioned against aproximal edge of the nose cone 218 thereby serving as a smoother andless traumatic contact surface.

With reference back to the embodiment of FIG. 13, the delivery system100 can include a tether retention member 134. The tether retentionmember 134 can be attached to the inner retention shaft 124. As shown inthe illustrated embodiment, the tether retention member 134 can be aC-lock having an opening through which a tether 136 can pass. In orderto retain the tether 136 within the tether retention member 134, the end138 of the tether 136 can be sized and shaped such that the end 138 isprevented from passing through the opening of the tether retentionmember 134. For example, the end 138 of the tether 136 can be knottedsuch that at least one dimension of the end 138 prevents the end 138from passing through the opening. In the illustrated embodiment, thetether 136 can be released from the tether retention member 134 bypassing the tether 136 radially away from and over the tether retentionmember 134. The tether 136 can be tensioned and angled such that thetether 136 would pass over the tether retention member 134 when tetherretention member 134 is uncovered from the lock 129 (not shown). Itshould be understood that other mechanisms can be used for tetherretention assembly 128 in lieu of the lock and tether retention member134 including, but not limited to, clamps which engage the tether 136.Although not shown, the tether 136 can engage at least a portion of theprosthesis, such as the second end of the prosthesis. For example, insome embodiments, the tether can wrap around at least some portion ofthe prosthesis and extend at least proximally through at least the outerelongate hollow member 116 and/or the outer elongate hollow member shaft114. The end opposite end 138 can be attached to a component of thedelivery system 100 such that the tether 136 can be retracted into thedelivery system 100 upon release of the tether 136 from the tetherretention assembly 128.

The embodiments of FIGS. 14-23 illustrate steps of a method of operatingthe delivery system 100 and releasing an intralumenal frame assembly,such as implant 30, to intralumenal tissue at an in situ targetlocation. The steps of this method can be carried out while theintralumenal frame assembly is in a radially compacted state within anouter member, such as outer elongate hollow member 116. In someembodiments, the longitudinal axis of the frame assembly, which runsbetween the first and second ends of the intralumenal frame assembly,can be parallel to and/or concentric with the longitudinal axis of oneor more shafts of the delivery system 100. The steps of this method canbe used to transapically deliver a replacement heart valve to a mitralvalve location.

With reference first to the step of FIG. 14, the delivery system 100 isshown in a preliminary configuration with the outer elongate hollowmember 116 covering the implant (not shown) and adjacent to the nosecone 118. In this configuration, the delivery system 100 has arelatively compact form factor which facilitates delivery of the implantto the in situ target location. As shown in the illustrated embodiment,the outer elongate hollow member 116 can remain wholly outside theintroducer sheath 112 in this configuration.

With reference next to the step of FIG. 15, once the delivery system 100has positioned the implant at the in situ target location, the outerelongate hollow member 116 can be moved relatively away from the nosecone 118, either by proximally retracting the outer elongate hollowmember 116 and/or distally advancing the nose cone 118, to uncover atleast a portion of the implant 30. As shown in the illustratedembodiment, the outer elongate hollow member 116 can also be movedrelatively toward the introducer sheath 112, either by proximallyretracting the outer elongate hollow member 116 and/or distallyadvancing the introducer sheath 112, such that the outer elongate hollowmember 116 is partially received within the introducer sheath 112.

With reference next to the step of FIG. 16, the outer elongate hollowmember 116 can be further moved relatively away from the nose cone 118to further uncover the implant 30 and/or relatively toward theintroducer sheath 112. As shown in the illustrated embodiment, thesecond end 31 of the implant 30 has been partially uncovered with boththe outer elongate hollow member 116 and the tether 136 restraining theradial dimension of the frame of the implant 30. It should be noted thatthe first end 33 of the implant 30 can remain covered by the nose cone118 during this step such that the first end 33 remains in a radiallycompacted state.

With reference next to the step of FIG. 17, the outer elongate hollowmember 116 can be further moved relatively away from the nose cone 118thereby further uncovering the implant 30 and/or relatively toward theintroducer sheath 112. As shown in the illustrated embodiment, thesecond end 31 of the implant 30 has been fully uncovered. Moreover, asshown in the illustrated embodiment, the second end 31 of the implant 30has at least partially expanded in the radial dimension with anchors 34having been flipped to extend distally away from the second end 31 ofthe implant 30. The tether 136 can continue to at least partiallyrestrain the radial dimension of the second end 31 and canadvantageously reduce the speed at which the second end 31 radiallyexpands. In some embodiments, the tether 136 can be designed such thatthe second end 31 remains in the fully compacted state when the secondend 31 is fully uncovered. It should be noted that the end (not shown)of the tether 136 remains attached to the tether retention assembly 128.During this step, tension in the tether 136 can be reduced such that thesecond end 31 of the implant 30 can be further radially expanded.

With reference next to the step of FIG. 18, the lock 129 has been movedrelatively away from the tether retention member 134 to release the end138 of the tether 136. In so doing, the second end 31 of the implant 30is allowed to further radially expand. It should be noted that the firstend 33 of the implant 30 can remain covered by the nose cone 118 duringthis step such that the first end 33 remains in a radially compactedstate. With reference next to the step of FIG. 19, the tether 136 andend 138 can be retracted into the delivery system 100.

With reference next to the step of FIG. 20, the inner retention member132 and/or the first end 33 of the implant 30 can be moved relativelyaway from the nose cone 118 such that the first end 33 of the implant 30can radially expand. This can be achieved by either distally moving thenose cone 118 relative to the inner retention member 132 and/or movingthe inner retention member 132 proximally relative to the nose cone 118.With reference next to the step of FIG. 21, the plug 126, attached tothe plug shaft 120, can be moved relatively toward the nose cone 118 toengage the nose cone 118. The plug 126 and/or plug shaft 120 can covermultiple of the inner components to facilitate extraction of thedelivery system 100 from the body after delivery of the implant 30 tothe in situ location. As shown in the step of FIG. 22, the outerelongate hollow member 116 can be further moved relatively toward theintroducer sheath 112. As shown in the step of FIG. 23, various othercomponents of the delivery system 100 can be moved relatively toward theintroducer sheath 112 to reduce the form factor of the delivery systemand further facilitate extraction of the delivery system 100 from thebody. FIG. 24 illustrates the implant 30 positioned within a nativevalve, such as a native mitral valve.

With reference to FIG. 31, an embodiment of a delivery device or system1010 is shown. The delivery system can be used deploy a prosthesis, suchas a replacement heart valve, within the body. The illustratedembodiment comprises an elongate, delivery system configured to beadvanced through a patient's vasculature in a percutaneous deliveryapproach. The delivery system 1010 can be rigid and yet flexible to beable to pass through the vasculature while also navigating thecurvosities of the same. While the delivery system 1010 is described inconnection with a percutaneous delivery approach, and more specificallya transfemoral delivery approach, it should be understood that featuresof delivery system 1010 can be applied to any other delivery systemdescribed herein, including delivery systems 10, 100, 200 which aredescribed in connection with a transapical delivery approach. Moreover,features of delivery systems 10, 100, 200 can be applied to deliverysystem 1010.

The delivery system 1010 can include an elongate shaft assembly 1012comprising a proximal end and a distal end, wherein a handle 1014 iscoupled to the proximal end of the assembly 1012. The elongate shaftassembly 1012 can be used to hold the prosthesis for advancement of thesame through the vasculature to a treatment location. The elongate shaftassembly 1012 can include an implant retention area 1016 that can beused for this purpose. In some embodiments, the elongate shaft assembly1012 can hold an expandable prosthesis in a compressed state at implantretention area 1016 for advancement of the prosthesis within the body.The elongate shaft assembly 1012 may then be used to allow controlledexpansion of the prosthesis at the treatment location. The implantretention area 1016 is shown at the distal end of the delivery device,but may also be at other locations.

The elongate shaft assembly 1012 can include one or more subassembliessuch as an inner assembly 1018, a mid shaft assembly 1020, and an outersheath assembly 1022, as will be described in more detail below. Theinner assembly 1018, mid shaft assembly 1020, and outer sheath assembly1022 can be configured to deliver a prosthesis positioned within theimplant retention area 1016 to a treatment location. One or more of thesubassemblies can then be moved to allow the prosthesis to be releasedat the treatment location. For example, one or more of the subassembliesmay be movable with respect to one or more of the other subassemblies.The handle 1014 can include various control mechanisms 1024, 1026 thatbe used to control the movement of the various subassemblies as willalso be described in more detail below. In this way, the prosthesis canbe controllably loaded onto the delivery device 1010 and then laterdeployed within the body.

With continued reference to the subassemblies of the elongate shaftassembly 1012, FIGS. 32 and 33 respectively illustrate an exploded andcross-sectional view of the same. The inner assembly 1018 may be anelongate member, and in some embodiments, may have a nose cone 1028 onits distal end. The nose cone can be made of polyurethane for atraumaticentry and to minimize injury to venous vasculature. The nose cone canalso be radiopaque to provide for visibility under fluoroscopy. Nosecone 1028 can share features of other nose cones described herein, suchas nose cones 28, 118, 1128.

The inner assembly 1018 may include a lumen 1030 sized and configured toslidably accommodate a guidewire so that the delivery device 1010 can beadvanced over the guidewire through the vasculature. The inner assembly1018 may also be a steerable catheter which may or may not need or use aguidewire.

The inner assembly 1018 can comprise a tube, such as a hypodermic tubeor hypo tube 1032. The tube can be made from one of any number ofdifferent materials including nitinol, stainless steel, and medicalgrade plastics. The tube can be a single piece tube or multiple piecesconnected together. Using a tube made of multiple pieces can allow thetube to provide different characteristics along different sections ofthe tube, such as rigidity and flexibility. For example, in someembodiments it can be desirable, and/or needful, for the delivery device1010 to have greater flexibility at the distal end of the device, whereflexibility is not as necessary for the proximal end.

In some embodiments a first segment made of a hypo tube 1032 can extendalong a majority of the length of the inner assembly. For example, theillustrated metal hypo tube 1032 extends from a luer fitting 1062 withinthe handle 1016 (FIGS. 36A-C) at the proximal end towards the distal endup until a second segment 1034 of the inner assembly 1018 before theimplant retention area 1016. The hypo tube 1032 can provide columnstrength (pushability) to the inner assembly. The second segment 1034 ofthe inner assembly 1018 can be made of a more flexible material. Forexample, the second segment can comprise a wire 1034 such as amulti-stranded wire, wire rope, or wire coil. The wire 1034 can surrounda more flexible tube, such as a plastic tube, or it may be formed as atube without any additional inner materials or core. Thus, in someembodiments, the wire 1034 can be a hollow core wire rope. The wire 1034can provide the inner assembly 1018 with strength, similar to the hypotube, but it can also provide more flexibility to allow for navigatingthe curvosities of the vasculature, such as within the heart.

In some embodiments, the wire 1034 extends distally from the hypo tube1032 to the nose cone 1028. In some embodiments, the inner assembly 1018can include a third segment 1036. The third segment can be positioned atthe implant retention area 1016 and between the second segment 1034 andthe nose cone 1028. For example, the third segment can comprise a secondwire 1036 such as a multi-stranded wire, wire rope, or wire coil. Thesecond wire 1036 can surround a more flexible tube, such as a plastictube, or it may be formed as a tube without any additional innermaterials or core. The second wire 1036 may also be a hollow core wirerope.

In some embodiments, the second wire 1036 can have an outer diametersmaller than the first wire 1034. As the second wire is positioned atthe implant retention area 1016, it can be desirable that the secondwire 1036 have as small an outer diameter as possible, to reduce thesize of the delivery device loaded with a prosthesis. The prosthesis maybe able to provide some of the desired rigidity or strengthcharacteristics of the delivery device at the implant retention area1016 and this may allow the segment 1036 to have an even smaller outerdiameter.

In some embodiments, the third segment 1036 can comprise a plastic tube.The plastic tube can extend from the nose cone 1028 to the first segment1032. The second segment 1034 can surround the third segment 1036 and bepositioned between the first segment 1032 and the implant retention area1016. For example, the second segment 1034 can be a hollow core wirerope that surrounds the third segment 1036.

The inner assembly 1018 can also include a prosthesis retentionmechanism such as an inner retention ring 1038 that can be used toengage with the prosthesis. The inner retention ring 1038 can sharefeatures with other retention members, such as inner retention members132, 232. Examples of prostheses that may be engaged on the prosthesisretention mechanism when the delivery device 1010 is used to deliver areplacement heart valve are described in U.S. Pat. Nos. 8,403,983,8,414,644, 8,652,203 and U.S. Patent Publication Nos. 2011/0313515,2012/0215303, 2014/0277390, 2014/0277422, 2014/0277427, the entirety ofthese patents and publications are hereby incorporated by reference andmade a part of this specification. For example, the inner retention ring1038 can include a plurality of slots configured to engage with strutson the prosthesis. The inner retention ring 1038 can be mounted on thetube of the inner assembly 1018, such as at the junction of the distalend of the second segment 1034 and the proximal end of the third segment1036. The inner retention ring 1038 can also be part of the implantretention area 1016, and may be at the proximal end of the implantretention area 1016.

Struts or other parts of a prosthesis can be engaged with the innerretention ring 1038 and an outer retention member can cover both theprosthesis and the inner retention ring 1038 to secure the prosthesis onthe delivery device 1010. This outer retention member can be part of oneof the other one or more subassemblies of the elongate shaft assembly1012.

In the illustrated embodiment, the outer retention member is a supporttube or outer retention ring 1040 which is part of the mid shaftassembly 1020. The mid shaft assembly 1020 can slide over the innerassembly 1018 and the outer retention ring 1040 can slide over the innerassembly 1018 and the inner retention ring 1038 to encircle the innerretention ring 1038. In this way the outer retention ring 1040 can beused to help secure a prosthesis to or release it from the deliverydevice 1010. The inner and outer retention rings and the delivery devicegenerally may be similar to those disclosed in U.S. Pat. Nos. 8,414,644and 8,652,203, the entire contents of both of which are herebyincorporated by reference herein and made a part of this specification.This is inclusive of the entire disclosure, including other apparatusesand methods described therein, and is not in any way limited to thedisclosure of the inner and outer retentions and/or the delivery device.

Like the inner assembly 1018, the mid shaft assembly 1020 can be asingle piece tube or multiple pieces connected together to providedifferent characteristics along different sections of the tube. As hasbeen mentioned, in some embodiments it can be desirable, and/or needful,for the delivery device 1010 to have greater flexibility at the distalend of the device, where flexibility is not as necessary for theproximal end. The illustrated mid shaft assembly 1020 has a firstsegment 1042, a second segment 1044, and a third segment 1040 being theouter retention ring 1040. The first segment 1042 is preferably formedof plastic, but could also be a metal hypo tube or other material.

The second segment 1044 is shown including a metal coil spring 1046which is connected to the outer retention ring 1040 at one end and tothe plastic tube 1042 at the other end. FIG. 34 shows an exploded viewof the mid shaft assembly 1020 including the components of the secondsegment 1044. As shown, the second segment 1044 can include an innermember 1048 and an outer member 1046. The mid shaft assembly 1020 alsocan include various coupling members 1050, 1052, 1054 that can be usedto connect the different first and third segments to the second segment,as well as to connect the inner 1048 and outer 1046 members.

One of the inner 1048 and outer 1046 members can be a compression memberand the other can be a tension member. The compression member and thetension member can be concentrically arranged. They are also both highlyflexible. As shown, the outer member is a coil spring 1046 and the innermember is a braided wire 1048. A length of a coil spring or a braidedwire can be highly flexible and can be moved in many directions. Forexample, they can both be twisted around a full 180 degrees or more,depending on the length of the material. The compression member and thetension member can provide a balance of forces with flexibility withoutover stretching or too much shortening.

It will be understood that a compression member by itself, such as acoil spring and/or HDPE tube, can provide certain benefits, but also hascertain draw backs. A compression member can apply a distally directedforce on the inner retention member 1038 and can oppose proximallydirected forces. But, compression members do not generally perform wellunder tension. For example, a spring can stretch when under tension. Itwill be understood, that when the mid shaft assembly 1020 is being slidaway from the inner retention member 1038, for example, to release aprosthesis, it could experience resistance that could cause the springto stretch such that the prosthesis is not released. Adding a tensionmember, such as a braided wire, can prevent this from occurring as thetension member can limit the amount of stretching of the compressionmember. The braided wire helps pull back the spring, but also has somegive to expand and compress with the spring. The tension member canprovide the required flexibility but resist stretching. Thus thecompression and tension members can beneficially allow for increasedflexibility while also providing more reliable implant releasecapabilities.

As has been mentioned, the mid shaft assembly 1020 can include variouscoupling members 1050, 1052, 1054. A first coupling member 1050 can beused to connect the first 1042 and second 1044 segments. The firstcoupling member 1050 can be made of metal or plastic and is shown with aplug end to form a friction fit with the first member 1042. The secondmember can be fastened to the first coupling member 1050 such as byadhesive or ultrasonic welding. In some embodiments the inner member canattach to an inside surface of the first coupling member 1050 and theouter member 1046 can attach to an outside surface of the first couplingmember 1050. The second coupling member 1052 can attach to the inner andouter members in a similar manner. The third segment 1040 can beattached to the second segment 1044 by the interaction of the second1052 and third 1054 coupling members. The third coupling member 1054 canbe received in the second coupling member 1052 via snap fit connectionwith the third segment securely positioned between the second and thirdcoupling members. It will be understood that this is just one example ofhow the various segments could be connected.

In some embodiments the sheath assembly 1012 has only two subassemblieswhich can be the inner 1018 and mid shaft 1020 assemblies as have beendescribed. In some such embodiments, though the outer retention ring1040 is shown as a relatively short ring, it could also be elongate andcould extend from the inner retention ring 1038 to the nose cone 1028when in a fully advanced position. In addition, the outer member 1046such as a coil spring could be covered with a sheath such as sheath madeof polytetrafluoroethylene (PTFE) or expanded polytetrafluoroethylene(ePTFE).

Returning now to FIGS. 32 and 33, the outer sheath assembly 1022 will bedescribed. The outer sheath assembly 1022 is disposed so as to beslidable over the inner assembly 1018 and the mid shaft assembly 1020Like the inner assembly 1018 and the mid shaft assembly 1020, the outersheath assembly 1022 can be a single piece tube or multiple piecesconnected together to provide different characteristics along differentsections of the tube. As has been mentioned, in some embodiments it canbe desirable, and/or needful, for the delivery device 1010 to havegreater flexibility at the distal end of the device, where flexibilityis not as necessary for the proximal end. The illustrated outer sheathassembly 1022 has a first segment 1056, a second segment 1058, and athird segment 1060.

The first segment 1056 is a tube and is preferably formed plastic, butcould also be a metal hypo tube or other material. In some embodiments,the tube 1056 is formed of a polyether block amide (PEBA) or other typeof a thermoplastic elastomer (TPE). In particular the tube 1056 can be awire braided reinforced PEBA which can enhance pushability andtrackability.

The second segment 1058 can be a metal hypo tube which in someembodiments may be cut or have slots. The hypo tube can providestructural rigidity, while the cuts can provide for flexibility in thehypo tube. The second segment can be a laser cut nitinol tube designedto allow adequate flexibility but with sufficient column strength toprovide finite control for stepwise retraction of the outer sheathduring deployment. For example, the remaining material can form a seriesof interconnected “H”s that are offset by 90 degrees. As anotherexample, the hypo tube can be cut into a series of rings with smallconnecting members extending between the rings. For example two equallyspaced connecting members can be used to connect two rings and thesubsequent connecting members can be offset 90 degrees. Other numbers ofconnecting members such as one, two, three, four, etc. can also be used.

The tube 1058 can be covered or encapsulated with a layer of ePTFE,PTFE, or other material so that the outer surface of the outer sheathassembly is generally smooth.

The third segment 1060 can be a tube formed of a plastic or metalmaterial. In a preferred embodiment, the third segment is formed ofePTFE or PTFE. In some embodiments this sheathing material can berelatively thick to prevent tearing and to help maintain aself-expanding implant in a compacted configuration. In some embodimentsthe material of the third segment 1060 is the same material as thecoating on the cut hypo tube 1058.

Looking now to FIGS. 35A-C, the relative movements of the one or moresubassemblies of the elongate shaft assembly 1012 will be described.FIG. 35A shows the outer sheath assembly 1022 in its distal mostposition. The third segment 1060 of the outer sheath is shown in contactwith the proximal end of the nose cone 1028. In this position, aprosthesis can be held within the elongate shaft assembly 1012 foradvancement of the same through the vasculature to a treatment location.

Once at the desired location, the outer sheath assembly 1022 can beretracted proximally to expose a portion of or all of a prosthesis inthe implant retention area 1016. FIG. 35B illustrates the elongate shaftassembly 1012 with the outer sheath assembly 1022 can be retractedproximally to expose the entire implant retention area 1016. The midshaft assembly 1020 can then be retracted as shown in FIG. 35C. This canallow any portion of the prosthesis engaged between the inner retentionmember 1038 and the outer retention member 1040 to be released. In somedelivery methods this would be the last step to fully deploying theprosthesis such as replacement heart valve.

FIGS. 36A-C show the corresponding position of the control mechanismsand components at the handle from the configurations of FIGS. 35A-C. Tomove the outer sheath assembly 1022 between the advanced position (FIG.35A) and the retracted position (FIG. 35B), the control mechanism 1024is actuated. As shown, the control mechanism 1024 is a retraction knobthat is rotated. This causes a lead screw 1064 connected to the firstsegment 1056 of the outer sheath assembly 1022 to move proximally (FIG.36B). Then, to move the mid shaft assembly 1020, the control mechanism1026 is pulled backwards (FIG. 36C). Springs 1066 can be used to givefeedback to the user and to better control the movement of the mid shaftassembly 1020 to thereby provide a controlled release of the prosthesis.In addition, the springs 1066 can maintain a continuous extension forcebetween the inner assembly 1018 and the mid shaft assembly 1020 to keepthe inner retention member 1038 bottomed out inside the outer retentionmember 1040 so that the distal tip of the delivery device 1010 maintainsmaximum flexibility and freedom of motion and the prosthesis does notunlock and prematurely deploy.

Aspects of the handle 1014, can be used in conjunction with otherdelivery devices described herein, such as delivery devices 10, 100,200, 1100. For example, in some embodiments, the control mechanism 1024can be used with a lead screw 1064 as shown in FIGS. 36A and 36Bconnected to an outer elongate hollow member shaft 114, to controlmovement of the outer elongate hollow member shaft 114 and/or elongatehollow member 116 as shown in FIG. 9. Moreover, springs 1066 as shown inFIG. 36C can be operably coupled to the locking shaft 122 to controlmovement of the locking shaft 122 and/or lock 129 as shown in FIG. 11.For example, the springs 1066 can be used to bias locking shaft 122 in aretracted position such that actuation of a switch can cause the lockingshaft 122 to move towards the retracted position. This can, in someembodiments, facilitate release of the tether, wire or suture 32 fromthe tether retention assembly 128.

The handle can also include any number of luers that can allow allsubassemblies to be perfused with saline. The perfusion of saline caneliminate or reduce air embolism risk due to catheter use and can alsoprovide flushing capability for the delivery procedure.

Turning now to FIG. 37, an embodiment of a delivery device 1010 is shownwith a schematic representation of a prosthesis 1070, such as areplacement heart valve, within the implant retention area 1016. As hasbeen discussed, the outer retention ring 1040 and the outer sheath 1022can cooperate to hold the replacement heart valve 1070 in a compactedconfiguration. The inner retention ring 1038 is shown engaging thestruts 1072 at the proximal end of the heart valve 1070. For example,teeth 1068 on the inner retention ring 1038 can engage the struts 1072which may end in tabs on the proximal end of the heart valve 1070. Theouter retention ring 1040 can be positioned over the inner retentionring 1038 so that the proximal end of the replacement heart valve 1070is trapped therebetween, securely attaching it to the delivery device1010. The prosthesis 1070 can include one or more sets of anchors, suchas distal anchors 1080 and proximal anchors 1082. The prosthesis 1070may be similar to the replacement heart valves disclosed in U.S. Pat.Nos. 8,403,983, 8,414,644 and 8,652,203, and U.S. Patent PublicationNos. 2011/0313515, 2012/0215303, 2014/0277390, 2014/0277422,2014/0277427, the entirety of these patents and publications are herebyincorporated by reference and made a part of this specification.

The delivery device 1010 may be provided to users with a prosthesis 1070preinstalled. In other embodiments, the prosthesis 1070 can be loadedonto the delivery device shortly before use, such as by a physician ornurse.

Methods of use of the delivery device in connection with a replacementmitral valve will now be described. In particular, the delivery device1010 can be used in a method for percutaneous delivery of thereplacement mitral valve to treat patients with moderate to severemitral regurgitation. The below methods are just a few examples of thehow the delivery device may be used. It will be understood that thedelivery devices described herein can be used as part of other methodsas well.

As shown in FIG. 38, in one embodiment a guidewire 1076 can be placed inthe ipsilateral femoral vein 1074 and advanced to the right atrium. Atransseptal puncture using known techniques can then be performed toobtain access to the left atrium. The guidewire 1076 can then beadvanced in to the left atrium and then to the left ventricle. FIG. 38shows a guidewire 1076 extending from the ipsilateral femoral vein 1074to the left atrium 1078. A guidewire snare can be placed in thedescending aorta through the ipsilateral femoral artery. The guidewirecan be advanced into the ascending aorta and then the snare can be usedto snare the guidewire. The guidewire snare can then be withdrawn toexternalize the guidewire from the ipsilateral femoral artery. Thephysician now has access to both ends of the guidewire. It will beunderstood that one or more introducer sheaths, catheters and/orguidewires may need to be used to get a guidewire externalized at boththe ipsilateral femoral vein and the ipsilateral femoral artery. Inaddition, the initial guidewire discussed above may not be the same asthe ultimate externalized guidewire. As will be explained in more detailbelow, having an externalized guidewire can be useful for positioningthe delivery device, especially the distal end of the delivery device,and for helping the delivery device turn some corners. Some embodimentsmay not use an externalized guidewire. For example, a steerable cathetermay be used instead of the externalized guidewire.

With the guidewire in place, the delivery device 1010 can be advancedover the guidewire through the lumen 1030. The delivery device can thenbe advanced to the right atrium, through the septal puncture and theleft atrium and into the left ventricle. A steering snare may be used tohelp advance and position the delivery device correctly. In addition,tension can be applied to one end of the externalized guidewire to helpadvance and position the delivery device. These additional helps can beparticularly useful to get the delivery device to make the bend fromextending up into the right atrium and then extending down into the leftventricle.

The construction and flexibility of the delivery device can allow it tomake the relatively sharp turns described above, in particular the turnsfrom entering the right atrium to the septum and then from the septum tothe mitral valve. It should be understood that the bending experiencedby the delivery device especially between the right atrium and themitral valve are relatively complex and are generally not in a singleplane. This part of the delivery device may experience bending between110-180 degrees and typically between 130-160 degrees, of course this isdependent on the actual anatomy of the patient.

Though the entire elongate shaft assembly 1012 may be experiencing somebending or flex, typically it is predominately the second segments 1034,1044, 1058 of the subassemblies (FIG. 32) that will be experiencing mostof the bending. This can be both when making the turns as the deliverydevice is being advanced, and also when the prosthesis is beingpositioned at the mitral valve. The nose cone 1028 can also be flexibleand may be bent during turning and at various other times during theprocedure.

The second segments 1034, 1044, 1058 can have a bendable length that issubstantially aligned with one another. The second segments 1034, 1044,1058 may each have a bendable length of at least between about 3.5 to 4inches (8.9 to 10.2 cm). In some embodiments, the second segment 1058 ofthe outer sheath can have a bendable length of about 3⅝ inches (9.2 cm),the second segment 1044 of the mid shaft can have a bendable length ofabout 4¾ inches (12.1 cm), and the second segment of the inner assemblycan have a bendable length of about 5.5 to 6 inches (14 to 15.2 cm). Insome embodiments, the relative bendable lengths of the second segmentscan increase going from the outermost subassembly to the innermostsubassembly of the elongate shaft assembly 1012.

The delivery device can include a radially-compacted replacement mitralvalve 1070 that has been preloaded within the implant retention area1016. With the distal end of the delivery device 1010 within the leftventricle, the operator can begin to deploy the replacement mitralvalve. Using one or more of the delivery device, the guidewire, and asnare, the distal end of the delivery device can be positioned to besubstantially perpendicular to the plane of the mitral annulus. It canalso be positioned so that the tips of the distal most anchors 1080 onthe replacement valve 1070 are midway between a plane formed by the topof the mitral annulus and a plane formed by the tops of the papillaries.The chordae tendineae extend between the native leaflets attached to themitral annulus and the papillaries.

The user can then begin rotating the retraction knob 1024 to retract theouter sheath assembly 1022 until the distal most anchors 1080 begin toextend out from the outer sheath assembly 1022. Retracting the outersheath assembly 1022 can allow the valve to self-expand. In someembodiments, the outer sheath assembly 1022 can be at least partiallyretracted. The distal anchors 1080 can then be positioned between thechordae tendineae. The angle and depth of the distal anchors 1080 thenbe adjusted to engage one or more leaflet of the mitral valve. Thus, thedistal anchors 1080 can be move back towards the annulus and in someembodiments may engage the leaflet and/or the ventricular side of theannulus. At the same time, the proximal end of the replacement heartvalve 1070 can remain retained by the delivery device in an at leastpartially radially compacted state. This can allow the position of thereplacement heart valve 1080 to still be readily adjusted.

In some embodiments, the distal anchors 1080 can be positioned first atone side of the left ventricle to engage the chordae tendineae and onevalve leaflet before engaging the other side and the other leaflet. Asthe mitral valve is a bicuspid valve, the delivery device 1010 can beused to attach the distal anchors 1080 first to the posterior leafletand then to anterior leaflet. This second part can be done after thereplacement heart valve 1070 is expanded or further expanded by furtherretracting the outer sheath assembly 1022.

In some embodiments, the entrance route of the delivery device 1010 intothe left atrium 1078 can bias the delivery device 1010 towards one sideof the mitral valve. For example, the delivery device 1010 may be biasedtowards the posterior leaflet of the mitral valve. This can facilitatesecuring the distal anchors 1080 to the posterior side or the posteriorleaflet first, prior to expanding or further expanding the replacementheart valve 1070. The distal anchors 1080 can then be secured to theanterior side of the mitral valve or to the anterior leaflet.

After the distal anchors 1080 are released, the delivery device 1010 andreplacement heart valve 1080 can be moved proximally, which in someembodiments, causes the distal anchors to engage the native leafletsand/or native valve annulus. In addition to physically moving thedelivery device, this may also be done by pushing the guidewire from thevenous side towards the mitral annulus. Once the distal anchors 1080 areproperly placed, the delivery device 1010 can then release the proximalanchors 1082 and the proximal end of the replacement heart valve 1070.This can allow further self-expansion of the replacement heart valve1070 so that the proximal anchors 1082 engage the upstream or atrialside of the native annulus, and the replacement heart valve 1070 isdeployed in operational condition. This can be by fully retracting theouter sheath assembly 1022, such as by rotating the control knob 1024,until the replacement valve 1070 has reached its fully expanded state.

The outer retention ring 1040 can then be moved away from the innerretention ring 1038 to release the proximal end of the replacement valve1070 from the delivery device 1010. This can be done by moving thecontrol mechanism 1026 on the handle 1014 downward which is connected tothe outer retention ring 1040. The proximal anchors 1082 can flareradially outward under the self-expansion force of the valve 1070 andengage with the upstream or atrial side of the native mitral valveannulus. Foreshortening of the valve 1070 can cause the distal andproximal anchors to move towards one another to securely grasp thenative mitral valve annulus and the leaflets between their opposinglydirected anchor tips, and the replacement heart valve 1070 is fully andsecurely installed as can be seen in FIG. 39. The delivery device 1010can then be removed from the body.

It will be understood that in some embodiments the replacement heartvalve 1070 may not be self expanding, and the partial and fulldeployment may be accomplished by one or more inflatable balloons or thelike. In addition, one of more inflatable balloons may be a part of thedelivery device, such as part of the inner assembly 1018 and canpositioned at the implant retention area 1016 as part of the thirdsegment 1036.

Looking at FIG. 39, a schematic representation of the replacement heartvalve 1070 is depicted installed in a human heart 1084. The heart isshown in cross-section, and represents typical anatomy, including a leftatrium 1078 and left ventricle 1086. The left atrium 1078 and leftventricle 1086 communicate with one another through a mitral annulus1098. Also shown schematically in FIG. 39 is a native anterior mitralleaflet 1090 having chordae tendineae 1092 that connect a downstream endof the anterior mitral leaflet 1090 and to the left ventricle 1086.

As shown, the replacement heart valve 1070 is disposed so that themitral annulus 1098 is between the distal anchors 1080 and the proximalanchors 1082. All or most of the replacement heart valve 1070 extendsinto the left atrium 1078. The portion of the replacement heart valve1070 disposed upstream of the annulus 1098 (toward the left atrium) canbe referred to as being positioned supra-annularly. The portiongenerally within the annulus 1098 is referred to as positionedintra-annularly. The portion downstream of the annulus is referred to asbeing positioned sub-annularly (toward the left ventricle). In theillustrated embodiment, only a part of the foreshortening portion ispositioned intra-annularly or sub-annularly, and the rest of thereplacement heart valve 1070 is supra-annular.

Replacement heart valves can be delivered to a patient's heart mitralvalve annulus in various ways, such as by open surgery,minimally-invasive surgery, and percutaneous or transcatheter deliverythrough the patient's vasculature.

Looking now at FIGS. 40A-B, another embodiment of a delivery device 1110is shown. The delivery device 1110 can function in a similar manner tothat described above. The delivery device 1110 can include componentswhich share similar structure to those of other delivery devicesdescribed herein, such as delivery devices 10, 100, 200, 1010. Forexample, such components can include, but are not limited to, elongateshaft assemblies 1012, 1112, handles 1014, 1114, implant retention areas1016, 1116, inner assemblies 1018, 1118, mid shaft assemblies 1020,1120, outer sheath assemblies 1022, 1122 control mechanisms 1024, 1026,1124, 1126, nose cones 28, 118, 1028, 1128, hypo tubes 1032, 1132,segments 1036, 1136, inner retention rings and mechanisms 132, 232,1038, 1138, outer retention rings 1040, 1140, segments 1042, 1044, 1142,1144, outer members 1046, 1146, segments 1058, 1060, 1158, 1160 and/orlead screws 1064, 1164.

As shown in the illustrated embodiment, a primary difference between thedelivery device 1010 and the delivery device 1110 is the length of theelongate shaft assemblies 1012, 1112. It will be appreciated that ashort elongate shaft assembly 1112 can be more easily used in an openheart procedure or other more direct procedures than the percutaneousprocedure starting at the leg that has been described above with respectto delivery device 1010. For example, the delivery device 1110 can beused in procedures such as a transapical procedure as described above.At the same time, the delivery device 1110 can still be relativelyflexible to allow, for example, advancement through the pulmonary veinsor the wall of the left atrium and then bending of the delivery devicefor proper placement at the mitral valve. The delivery device 1110 canshare features with delivery devices described herein, such as deliverydevices or systems 10, 100, 200, 1010.

The construction and flexibility of the delivery device can allow it tomake the relatively sharp turns described above. It should be understoodthat the bending experienced by the delivery device may be relativelycomplex and are generally not in a single plane. This part of thedelivery device may experience bending between 65-130 degrees; of coursethis is dependent at least partially on the actual anatomy of thepatient.

Though the entire elongate shaft assembly 1112 may be experiencing somebending or flex, it is predominately the second segments 1134, 1144,1158 of the subassemblies that will be experiencing most of the bending.This is both when making the turns as the delivery device is beingadvanced, and also when the prosthesis is being positioned at the mitralvalve. The nose cone 1128 can also be flexible and may be bent duringturning and at various other times during the procedure. In someembodiments of the delivery device 1110, the second segments can extendfrom the first segments to the handle. Some subassemblies may or mayinclude the first segments described above with respect to the deliverydevice 1110. The second segments 1134, 1144, 1158 can have a bendablelength that is substantially aligned with one another. The secondsegments 1134, 1144, 1158 may each have bendable lengths similar tothose described above for second segments 1034, 1044, 1058, though theymay also be longer or shorter. For example the second segment 1158 ofthe outer sheath assembly may extend from the first segment 1160 to thescrew 1164, while the other second segments 1134, 1144 may be shorter.

It will be understood that the delivery devices, such as deliverydevices 10, 100, 200, 1010, 1110 can include many additional featuressimilar to those described in U.S. Pat. Nos. 8,414,644 and 8,652,203,the entirety of each of which are hereby incorporated by reference andmade a part of this specification. For example, the nose cone caninclude a prosthesis retention mechanism such as an inner retention ringthat can be used to engage with the prosthesis as may be described inthese applications. Struts or other parts of a prosthesis can be engagedwith the inner retention ring and the nose cone can cover both theprosthesis and the inner retention ring to secure the prosthesis on thedelivery devices 10, 100, 200, 1010, 1110. In addition, the deliverydevice can be used in delivery methods similar to those described in theabove referenced patents and application.

Any value of a threshold, limit, duration, etc. provided herein is notintended to be absolute and, thereby, can be approximate. In addition,any threshold, limit, duration, etc. provided herein can be fixed orvaried either automatically or by a user. Furthermore, as is used hereinrelative terminology such as exceeds, greater than, less than, etc. inrelation to a reference value is intended to also encompass being equalto the reference value. For example, exceeding a reference value that ispositive can encompass being equal to or greater than the referencevalue. In addition, as is used herein relative terminology such asexceeds, greater than, less than, etc. in relation to a reference valueis intended to also encompass an inverse of the disclosed relationship,such as below, less than, greater than, etc. in relations to thereference value.

While certain embodiments have been described, these embodiments havebeen presented by way of example only, and are not intended to limit thescope of the disclosure. Indeed, the novel methods and systems describedherein may be embodied in a variety of other forms. Furthermore, variousomissions, substitutions and changes in the systems and methodsdescribed herein may be made without departing from the spirit of thedisclosure. The accompanying claims and their equivalents are intendedto cover such forms or modifications as would fall within the scope andspirit of the disclosure. Accordingly, the scope of the presentdisclosure is defined only by reference to the claims presented hereinor as presented in the future.

Features, materials, characteristics, or groups described in conjunctionwith a particular aspect, embodiment, or example are to be understood tobe applicable to any other aspect, embodiment or example described inthis section or elsewhere in this specification unless incompatibletherewith. All of the features disclosed in this specification(including any accompanying claims, abstract and drawings), and/or allof the steps of any method or process so disclosed, may be combined inany combination, except combinations where at least some of suchfeatures and/or steps are mutually exclusive. The protection is notrestricted to the details of any foregoing embodiments. The protectionextends to any novel one, or any novel combination, of the featuresdisclosed in this specification (including any accompanying claims,abstract and drawings), or to any novel one, or any novel combination,of the steps of any method or process so disclosed.

Furthermore, certain features that are described in this disclosure inthe context of separate implementations can also be implemented incombination in a single implementation. Conversely, various featuresthat are described in the context of a single implementation can also beimplemented in multiple implementations separately or in any suitablesubcombination. Moreover, although features may be described above asacting in certain combinations, one or more features from a claimedcombination can, in some cases, be excised from the combination, and thecombination may be claimed as a subcombination or variation of asubcombination.

Moreover, while operations may be depicted in the drawings or describedin the specification in a particular order, such operations need not beperformed in the particular order shown or in sequential order, or thatall operations be performed, to achieve desirable results. Otheroperations that are not depicted or described can be incorporated in theexample methods and processes. For example, one or more additionaloperations can be performed before, after, simultaneously, or betweenany of the described operations. Further, the operations may berearranged or reordered in other implementations. Those skilled in theart will appreciate that in some embodiments, the actual steps taken inthe processes illustrated and/or disclosed may differ from those shownin the figures. Depending on the embodiment, certain of the stepsdescribed above may be removed, others may be added. Furthermore, thefeatures and attributes of the specific embodiments disclosed above maybe combined in different ways to form additional embodiments, all ofwhich fall within the scope of the present disclosure. Also, theseparation of various system components in the implementations describedabove should not be understood as requiring such separation in allimplementations, and it should be understood that the describedcomponents and systems can generally be integrated together in a singleproduct or packaged into multiple products.

For purposes of this disclosure, certain aspects, advantages, and novelfeatures are described herein. Not necessarily all such advantages maybe achieved in accordance with any particular embodiment. Thus, forexample, those skilled in the art will recognize that the disclosure maybe embodied or carried out in a manner that achieves one advantage or agroup of advantages as taught herein without necessarily achieving otheradvantages as may be taught or suggested herein.

Conditional language, such as “can,” “could,” “might,” or “may,” unlessspecifically stated otherwise, or otherwise understood within thecontext as used, is generally intended to convey that certainembodiments include, while other embodiments do not include, certainfeatures, elements, and/or steps. Thus, such conditional language is notgenerally intended to imply that features, elements, and/or steps are inany way required for one or more embodiments or that one or moreembodiments necessarily include logic for deciding, with or without userinput or prompting, whether these features, elements, and/or steps areincluded or are to be performed in any particular embodiment.

Conjunctive language such as the phrase “at least one of X, Y, and Z,”unless specifically stated otherwise, is otherwise understood with thecontext as used in general to convey that an item, term, etc. may beeither X, Y, or Z. Thus, such conjunctive language is not generallyintended to imply that certain embodiments require the presence of atleast one of X, at least one of Y, and at least one of Z.

Language of degree used herein, such as the terms “approximately,”“about,” “generally,” and “substantially” as used herein represent avalue, amount, or characteristic close to the stated value, amount, orcharacteristic that still performs a desired function or achieves adesired result. For example, the terms “approximately”, “about”,“generally,” and “substantially” may refer to an amount that is withinless than 10% of, within less than 5% of, within less than 1% of, withinless than 0.1% of, and within less than 0.01% of the stated amount. Asanother example, in certain embodiments, the terms “generally parallel”and “substantially parallel” refer to a value, amount, or characteristicthat departs from exactly parallel by less than or equal to 15 degrees,10 degrees, 5 degrees, 3 degrees, 1 degree, or 0.1 degree.

The scope of the present disclosure is not intended to be limited by thespecific disclosures of preferred embodiments in this section orelsewhere in this specification, and may be defined by claims aspresented in this section or elsewhere in this specification or aspresented in the future. The language of the claims is to be interpretedbroadly based on the language employed in the claims and not limited tothe examples described in the present specification or during theprosecution of the application, which examples are to be construed asnon-exclusive.

What is claimed is:
 1. As method of delivering an intralumenal frameassembly to intralumenal tissue at an in situ target location, themethod comprising: delivering an intralumenal frame assembly to the insitu target location while the frame assembly is in a radially compactedstate within an outer member, the frame assembly comprising a framehaving a first end, a second end and a longitudinal axis extendingbetween the first and second ends, the frame further comprising a tetherencircling at least a portion of the frame, the tether configured torestrain the radial dimension of the frame; at least partially removingthe outer member from the frame assembly, wherein the tether restrainsthe radial dimension of the frame after the outer member is at leastpartially removed; and releasing the tether from the frame to allow atleast a portion of the frame assembly to radially expand.
 2. The methodof claim 1, wherein releasing the tether from the frame allows thesecond end of the frame to radially expand while the first end of theframe remains radially restrained.
 3. The method of claim 2, furthercomprising radially expanding the first end of the frame after releasingthe tether to allow the second end of the frame to radially expand. 4.The method of claim 3, wherein the first end of the frame, prior toradial expansion, is restrained by a nose cone covering at least thefirst end of the frame.
 5. The method of claim 4, wherein the outermember is at least partially removed from the frame assembly by movingthe outer member relatively away from the nose cone.
 6. The method ofclaim 5, wherein the outer member is at least partially removed in aproximal direction from the frame assembly by moving the outer memberrelatively away from the nose cone.
 7. The method of claim 6, whereinthe intralumenal frame assembly comprises a plurality of anchors at itssecond end, wherein the plurality of anchors extend proximally away fromthe second end of the frame assembly as the outer member is movedproximally, and the plurality of anchors flip to extend distally awayfrom the second end of the frame assembly after the outer memberuncovers the plurality of anchors, and wherein the tether radiallyrestrains the frame assembly during flipping of the anchors.
 8. Themethod of claim 1, wherein the intralumenal frame assembly comprises areplacement heart valve.
 9. The method of claim 1, wherein theintralumenal frame assembly is delivered transapically to a mitral valvelocation.
 10. The method of claim 1, wherein the tether is restrainedprior to the releasing in a tether retention assembly comprising aC-lock.
 11. The method of claim 1, wherein the tether is restrainedprior to the releasing in a tether retention assembly comprising aninner component and an outer component, the outer component configuredto cooperate with the inner component to restrain the tether, whereinthe outer component is moveable relative to the inner component.
 12. Themethod of claim 1, wherein the first end of the frame, prior to radialexpansion, is restrained between a nose cone and an inner retentionring.
 13. The method of claim 12, wherein the inner retention ringtapers radially inwards towards a proximal end of the inner retentionring.
 14. The method of claim 13, further comprising proximallywithdrawing at least a portion of the inner retention ring into theouter member.
 15. The method of claim 12, wherein the inner retentionring comprises a cavity at least partially receiving a compressiblemember.
 16. The method of claim 12, wherein the inner retention ringcomprises a plurality of slots that receive the first end of the framewhen the frame assembly is delivered, wherein the first end of the framecomprises a plurality of struts having enlarged tabs.
 17. The method ofclaim 1, wherein the delivering is performed by a delivery systemcomprising a handle having a knob configured to translate the outermember.
 18. The method of claim 17, wherein the delivery systemcomprises a guide member having an aperture, and wherein the tetherextends through the aperture.
 19. The method of claim 17, wherein thedelivery system comprises the outer shaft, a locking shaft radiallyinwards of the outer shaft, an inner retention shaft radially inwards ofthe locking shaft, and a nose cone shaft radially inwards of the innerretention shaft.
 20. The method of claim 1, wherein the at leastpartially removing the outer member allows the portion of the frame toexpand to an intermediate expanded position and the releasing the tetherallows the portion of the frame to expand to a fully expanded position.